We have adopted recombinant DNA and related techniques to study the molecular biology of the cytochromes P-450 (P-450s), a family of enzymes central to the activation and detoxification of carcinogens and to the metabolism of xenobiotics and drugs. Our goal is to understand the structure and regulation of P-450 genes, to elucidate the molecular basis for the multiplicity of the P-450s and for the structural-functional relationships among them, and to determine the extent to which individual susceptibility of humans to cancer depends on the regulation of expression of specific P-450s. This year we have determined the detailed structure of a 3-methylcholanthrene-induced P-450 (MC-P-450) gene whose isolation we reported last year. We have also cloned and characterized cDNAs corresponding in sequence to the two most abundant forms of MC-P-450 mRNA in liver. We have determined the sizes of these two P-450 mRNAs and the peptides for which they code, and have quantitated them in control and induced tissues. We have also used these MC-P-450 cDNAs as hybridization probes to isolate the corresponding new P-450 genes from a library of the rat genome.